A-887826

A-887826 is a potent, selective, oral bioavailable and voltage-dependent Na(v)1.8 sodium channel blocker with an IC50 of 11 nM . A-887826 attenuates neuropathic tactile allodynia in vivo[1].

Signaling Pathways >> Membrane Transporter/Ion Channel >> Sodium Channel

Research Areas >> Neurological Disease

IC50: 11 nM (Na(v)1.8)[1]

A-887826 is approximately 3 fold less potent to block Na(v)1.2, approximately 10 fold less potent to block tetrodotoxin-sensitive sodium (TTX-S Na(+)) currents and is >30 fold less potent to block Na(v)1.5 channels[1]. A-887826 potently blocks tetrodotoxin-resistant sodium (TTX-R Na(+)) currents (IC50=8 nM) from small diameter rat dorsal root ganglion (DRG) neurons in a voltage-dependent fashion[1]. A-887826 effectively suppresses evoked action potential firing when DRG neurons are held at depolarized potentials and reversibly suppresses spontaneous firing in small diameter DRG neurons from complete Freund's adjuvant inflamed rats[1]. A-887826 (100 nM) shifts the mid-point of voltage-dependent inactivation of TTX-R currents by approximately 4mV without affecting voltage-dependent activation and do not exhibit frequency-dependent inhibition[1].

A-887826 (3-30 mg/kg; p.o.; 1 hour pre-treatment) significantly attenuates tactile allodynia in a rat neuropathic pain model[1]. Animal Model: Male Spraguee Dawley rats (200-300 g)[1] Dosage: 3 mg/kg, 10 mg/kg, 30 mg/kg Administration: Oral administration; 1 hour before testing; fourteen days after L5-L6 spinal nerve ligation Result: Produced a dose-dependent attenuation of tactile allodynia in this experimental pain model.

[1]. Zhang XF, et al. A-887826 is a structurally novel, potent and voltage-dependent Na(v)1.8 sodium channel blocker that attenuates neuropathic tactile allodynia in rats. Neuropharmacology. 2010 Sep;59(3):201-7.